Bilateral Proximal Forearm Transplantation: Case Report at 7 Years.

BACKGROUND: Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT. CASE PRESENTATION: A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force. RESULTS: Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year. CONCLUSIONS: Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.

Graft immunologic events in deceased donor kidney transplant recipients with preformed HLA-donor specific antibodies.

INTRODUCTION: Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center. PATIENTS AND METHODS: 246 KT were performed at our center between 01/2012 and 12/2015 and 100 KTR obtained from a DD were analyzed; 24% harbored DSA by SAB assay, MFI values >500 were considered positive. All recipients received thymoglobulin induction and generic tacrolimus-based maintenance therapy. Graft biopsies were performed by protocol on months 3 and 12 as well as per indication. The incidence of AMR and ACR was correlated with the existence of pretransplant DSA. RESULTS: Overall, 34% of patients developed an acute rejection episode, 54.2% in the DSA group versus 27.6% in the non-DSA group (p=0.032), and most of these events were detected as subclinical conditions in protocol biopsies. AMR events developed in 33.3% and 19.7% (p=0.176) in the DSA and the non-DSA groups, respectively. ACR events were found in 16.6% and 6.6% (p=0.127) in the DSA and non-DSA groups, respectively. Graft function was similar between groups at the end of the 1st year posttransplant and no immunological graft loss occurred. CONCLUSION: Despite the use of depleting induction therapy and adequate tacrolimus trough levels along with MMF and steroids, a high rate of rejection events was observed during the first year post-transplantation.

Anti-HLA-DQ antibodies are highly and independently related to the C1q-binding capacity of HLA antibodies.

The complement-binding capacity of anti-HLA antibodies (HLAabs) is recognized as a key pathogenic factor. The aim of this study is to describe the patient characteristics associated to the presence of C1q+ as well as those of the Abs per se when associated to C1q binding. METHODOLOGY: This is a cross-sectional, observational, descriptive study of patients with previous sensitizing factors and awaiting a kidney transplant (KT). We determined anti-HLA antibodies and their C1q binding capacity with the C1q assay. RESULTS: Among the 55 included patients, 26 (47.2%) had at least one C1q+ anti-HLAab. A previous transplant history, a greater number of HLAabs, a greater % of class I or class II PRA, the average MFI of all HLAabs, the MFI of the dominant HLAab and the HLAab antigenic specificities against HLA-B, -C and -DQ, all proved to be risk factors associated to the presence of C1q binding HLAabs (C1q+). In the total population, were detected 1268 HLAabs, 230 (18.1%) of which were C1q+. On multivariate analysis, both HLAabs against the HLA-DQ antigenic specificity (OR 9.82 95% CI 5.4-17.6, p<0.001) and the MFI documented by LABScreen®SAB (OR 1.2% CI 1.22-1.3, p<0.001), proved to be risk factors. CONCLUSION: Anti-HLA-DQ antibodies and the MFI (LABScreen®SAB) are highly and independently related to the C1q-binding capacity of HLA antibodies.

C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low Sensitivity When Predicting Flow Crossmatch.

The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80-259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27-19.68, P = 0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06-1.49, P = 0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85-100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3-100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity.

Impact of pretransplant exposure to allosensitization factors generating HLA antibodies in the Luminex era.

AIM: To identify the frequency of exposure to sensitizing factors and evaluate the risk ascribable to each sensitizing factor generating HLAabs measured by Luminex. METHODS: This is a retrospective cohort study that included 502 transplanted patients and 51 patients on the waiting list for a deceased donor graft. Patients were divided into 4 groups according to the %PRA: 0%, 1 to 19%, 20 to 49% and ≥50%. The OR attributable to each sensitizing factor or combination were calculated. RESULTS: Of the total 553 subjects, 53.5% were male, with an average age 35.42±12.96years. 69.1% were exposed to one or more sensitizing factors; 44.8% had %PRA class I≥1 and 38.9% had %PRA class II≥1. Independently or combined, sensitizing factors persist as a risk factor for the development of a %PRA >1%, >20% or >50%. After multivariate analysis, the three sensitizing factors remained significantly associated to HLAab development. CONCLUSIONS: In spite of using a most sensitive technique such as Luminex to measure the %PRA, a clear association persists between exposure to sensitizing factors and a high %PRA. The risk increases after exposure to more than one sensitizing factor.

C1q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity But Low Sensitivity When Predicting Flow Crossmatch.

In complement dependent cytotoxicity crossmatch negative renal transplant candidates with human leukocyte antigen donor-specific antibodies (DSA), both the presence of DSA C1q+ and the dominant DSA fluorescence were significantly associated with a positive flow cytometry crossmatch (FXM+). The C1q+ assay was highly specific, but had low sensitivity when predicting FXM+, so the clinical significance of a FXM+ in the absence of DSA C1q+ remains to be clarified in future studies.

Markers of inflammation before and after renal transplantation.

BACKGROUND: This study aims to compare serum C-reactive protein (CRP), interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal disease (ESRD) patients before versus after receiving renal transplantation (RT) and versus donors. METHODS: Serum samples from 37 ESRD patients (24 male, age 34+/-13 years) were collected before and after RT; in addition, samples from 31 donors were obtained at transplantation. CRP concentrations were measured using nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked immunoadsorbent assay. RESULTS: Ninety-two percent of recipients had a living donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with daclizumab. Thirteen percent had acute rejection and 16% chronic allograft nephropathy. All inflammation markers decreased 6 months after RT, but only CRP was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months: 3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1-2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6 (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18 months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45, P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not different in patients who had acute rejection episodes or chronic nephropathy. CONCLUSIONS: Compared with controls, patients displayed an inflammatory phenomenon before receiving RT. Serum CRP decreased significantly after RT, whereas TNFalpha and IL-6 increased.